ATP-binding cassette sub-family G member 5 and member 8 (ABCG5/ABCG8)

ATP-binding cassette sub-family G member 5 and member 8 (ABCG5/ABCG8) are half-transporters that function as an obligate heterodimer to mediate the efflux of neutral sterols [1, 2]. Primarily expressed on the apical membranes of hepatocytes and enterocytes, this complex is responsible for secreting cholesterol and plant sterols (phytosterols) into bile and the intestinal lumen [2, 3]. This process is a vital component of reverse cholesterol transport and serves as a primary defense against the accumulation of dietary xenosterols [1, 4]. Mutations in either ABCG5 or ABCG8 cause sitosterolemia, a rare autosomal recessive disorder marked by elevated plant sterol levels, tendon xanthomas, and accelerated atherosclerosis [1, 3]. Additionally, common genetic variants are significantly linked to an increased risk of gallstone disease due to excessive biliary cholesterol secretion [5]. While no direct small-molecule activators are currently in clinical use, the transporter is transcriptionally regulated by nuclear receptors such as LXR and FXR, making it a key focus for research into cardiovascular and metabolic therapies [4, 5].

Other names

Sterolin-1Sterolin-2STSLSTSL1GBD4Sterolin heterodimer

ABCG5 and ABCG8 form an obligate heterodimer that utilizes ATP hydrolysis to actively transport neutral sterols, such as cholesterol and phytosterols, across the apical membranes of hepatocytes and enterocytes into the bile and intestinal lumen, respectively [1, 2, 3].